Celecoxib Decreases the Need for Rescue Analgesics after Total Knee Arthroplasty: A Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of celecoxib after total knee arthroplasty. Keywords in the PubMed and Scopus databases were used to find article abstracts. Each included clinical trial was assessed using the Cochrane Collaboration risk of bias tool, and we extracted data on postoperative pain assessment using the Visual Analogue Scale (VAS) at rest, ambulation, and active range of motion, rescue analgesic intake, and adverse effects. Inverse variance tests with mean differences were used to analyze the numerical variables. The Mantel-Haenszel statistical method and the odds ratio were used to evaluate the dichotomous data. According to this qualitative assessment (n = 482), two studies presented conclusions in favor of celecoxib (n = 187), one showed similar results between celecoxib and the placebo (n = 44), and three clinical trials did not draw conclusions as to the effectiveness of celecoxib versus the placebo (n = 251). Moreover, the evaluation of the rescue analgesic intake showed that the patients receiving celecoxib had a lower intake compared to patients receiving a placebo (n = 278, I2 = 82%, p = 0.006, mean difference = -6.89, 95% IC = -11.76 to -2.02). In conclusion, the pooled analysis shows that administration of celecoxib alone results in a decrease in rescue analgesic consumption compared to a placebo after total knee surgery.

Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis.

Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes.

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein-protein and target-compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa's antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.

Pharmacological network study on the effect of 6-gingerol on cervical cancer using computerized databases.

Cervical cancer (CC) is the most frequent cancer in the female population worldwide. Although there are treatments available, they are ineffective and cause adverse effects. 6-gingerol is an active component in ginger with anticancer activity. This research aims to discover the mechanism by which 6-gingerol act as an anticancer agent on CC through a pharmacological network using bioinformatics databases. From MalaCard, Swiss Target Prediction, Comparative Toxicogenomics Database, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we obtained the target genes for 6-gingerol and CC and matched them. We got 26 genes and analyzed them in ShinyGO-0.76.3 and DAVID-Bioinformatics Resources. Then, we generated a protein-protein interaction network in Cytoscape and obtained 12 hub genes. Hub genes were analyzed in Gene Expression Profiling Interactive Analysis and TISIDB. In addition, molecular docking studies were performed between target proteins with 6-gingerol using SwissDock database. Finally, molecular dynamics studies for three proteins with the lowest interaction energy were implemented using Gromacs software. According to gene ontology results, 6-gingerol is involved in processes of apoptosis, cell cycle, and protein kinase complexes, affecting mitochondria and pathways related to HPV infection. CTNNB1 gene was negatively correlated with CD8+ infiltration but was not associated with a higher survival rate. Furthermore, the molecular docking study showed that 6-gingerol has a high binding to proteins, and the molecular dynamics showed a stable interaction of 6-gingerol to AKT1, CCNB1, and CTNNB1 proteins. Conclusion, our work helps to understand the anticancer activity of 6-gingerol in CC that should be studied experimentally.Communicated by Ramaswamy H. Sarma.

Analgesic Efficacy and Safety of Tapentadol Immediate Release in Bunionectomy: A Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of different doses of tapentadol immediate release (IR) and its adverse effects after a bunionectomy. Pubmed, Cochrane, Lilacs, Medline, and Imbiomed were used to identify abstracts of scientific publications related to the keywords of this systematic review (PROSPERO ID CRD42023437295). Moreover, the risk of bias in all included articles was assessed using the Cochrane Collaboration risk of bias tool. Data on the sum of pain intensity, total pain relief, global assessment, and adverse effects were extracted. The statistical method of inverse variance with means difference was used to evaluate the numerical data and the Mantel-Haenszel and Odd Ratio test to analyze the dichotomous data. In addition, the number needed to treat, the number needed to harm, and the 95% confidence intervals were calculated. A qualitative evaluation (n = 2381) was carried out according to the conclusions of the authors. Tapentadol (n = 1772) was more effective in relieving postoperative pain than the placebo (n = 609) after a bunionectomy. In addition, the analgesic efficacy of IR tapentadol (n = 1323) versus the placebo (n = 390) was evaluated in a total of 1713 patients using a global evaluation of the treatments. All three doses of IR tapentadol showed better results compared to the placebo after a bunionectomy. Finally, the adverse effects have a direct relationship with the dose, and the greatest number of adverse effects are most observed with tapentadol IR 100 mg (n = 2381). It is concluded that tapentadol IR (100 mg) leads to the best satisfaction score in this meta-analysis.

Inflammatory Determinants and Associated Morbidity in Hemodialysis Patients.

Hemodialysis deteriorates patients' physical, metabolic, and mental status. Clinical outcomes derived from inflammation determine a worse status but are less frequently identified. The objective of the study was to identify inflammatory determinants and the effect of SNP-related serum IL-6 and IL-10 levels on associated morbidity in hemodialysis. A sample of hemodialysis patients at IMSS Regional Hospital No.46 in Guadalajara (n = 85) were tested using the Malnutrition Inflammation Score (MIS) and Patient Health Questionnaire-9 (PHQ-9) to assess the associated morbidity. Serum cytokine levels were quantified by enzyme-linked immunosorbent assay (ELISA). The restriction fragment length polymorphism (RFLP) technique was used for analysis of IL-6-572C/G and IL-10-1082A/G. Using data visualization methods, we identified relevant determinants of inflammation. A simple regression model was constructed between predictors and targets with genotypes as covariates. Results showed malnutrition in 85.9% of patients and depressive symptoms in 50.6%. IL-10 was the most relevant inflammatory determinant, with regression coefficients (R2) between 0.05 and 0.11. The GG genotype of IL-10-1082 A/G evinced small effect on both clinical outcomes (δ of 0.35 and 0.37, respectively). Hemodialysis increases the associated morbidity, cytokines act as inflammatory determinants, and genetic variability contributes to the severity of clinical outcomes. Further studies need to refine the causal relationship between inflammation and CKD.

Molecular mechanism of curcumin on periodontitis: A pharmacological network study.

OBJECTIVE: This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy. METHODS: The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein-protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin. RESULTS: Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin. CONCLUSION: The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin.

Bioinformatic Analysis of the Effect of Silver Nanoparticles on Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is the most diagnosed cancer with the highest mortality rate each year globally. Although there are treatments for CRC, the development of resistance to therapies decreases the success of treatments. In vitro studies using the Caco-2 cell line have revealed the anticancer properties of silver nanoparticles (AgNPs) as a possible treatment for this disease. This study considered four researches that evaluated the proteomic profiles of cells of the Caco-2 line exposed to AgNPs. We performed a bioinformatics analysis to predict protein-protein interaction, hub genes, Gene Ontology (molecular function, biological process, and cellular components), KEGG pathways, analysis of expression, and immune cell infiltration. For these analyses, the STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases were used. The results in Gene Ontology show that AgNPs cause a deregulation of genes related to cell-cell adhesion, the cytoplasm, the centriole, and carbon metabolism. Hub genes were identified, including GADPH, ENO1, EEF2, and ATP5A1, which showed differential expression in patients with adenocarcinoma of the colon and rectum. Additionally, the expression of the hub genes and immune cells was correlated. It was found that ATP5A1 and ENO1 were positively correlated with the infiltration of CD4+ T lymphocytes in colon adenocarcinoma and a negative correlation between GADPH and PDIA3 with the infiltration of NK cells and CD4+ T lymphocytes in rectal adenocarcinoma, respectively. In conclusion, the administration of AgNPs causes an alteration of biological processes, cellular components, metabolic pathways, deregulation of hub genes, and the activity of immune cells leading to a potential anticancer effect.

Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis.

Introduction: Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.

Introducción: Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso.

Anticancer Activity of Selenium Nanoparticles In Vitro Studies.

Health systems worldwide consider cancer a disease that causes the highest number of deaths per year. The low efficacy of current cancer therapies has led other areas of science to search for new alternatives, including nanomaterial sciences. Selenium nanoparticles have anticancer activity, as revealed by in vitro tests performed on prostate, breast, cervical, lung, colorectal, and liver cancer cell lines. Studies attribute anticancer activity to the anti-metastatic effect due to the inhibition of migration and invasion processes. The antiproliferative effect is the low expression of molecules such as cyclin D1, cyclin E, and CDK2. In addition to the activation of cell apoptosis by caspase-dependent mechanisms, there is a low expression of anti-apoptotic proteins such as Bcl-2 and a high expression of the apoptotic proteins like Bax and Bad. Other studies attribute anticancer activity to the activation of cell necroptosis, where molecules such as TNF and IRF1 participate. The pharmacological potential of selenium nanoparticles depends primarily on the administered dose, particle size, and chemical composition. Furthermore, several studies have shown that the administration of these nanoparticles is safe due to their low toxicity in non-cancerous cells. In this review, the most relevant antecedents on the anticancer potential of selenium nanoparticles in prostate, breast, cervical, lung, liver, and colorectal cancer cell lines are discussed.

Innate and adaptive immunity of periodontal disease. From etiology to alveolar bone loss.

Periodontal disease refers to inflammation of the tissues that support the tooth. It is of multifactorial etiology. Innate and adaptive immune cells participate jointly through the release of their molecules and mechanisms of action in order to maintain homeostasis in periodontal tissues, so the host's immune response plays an essential role in defense against microorganisms. However, bacterial persistence and the dysregulation of the immune system as an exaggerated response can lead to the worsening of periodontal disease, leading to loss of gingival tissue and alveolar bone and thereby loss of teeth. Therefore, a better understanding of the cellular mechanisms involved in the development of periodontal disease is necessary to design new treatments and prophylactic measures in order to decrease the prevalence of this disease that afflicts a large part of the world population.

Tumour necrosis factor-alpha polymorphism -308 G/a and its protein in subjects with gingivitis.

OBJECTIVE: This study examined the association between tumour necrosis factor-alpha (TNF- α) (-308 G/A) polymorphism and gingivitis, and serum and salivary TNF- α levels, in a Mexican population. MATERIAL AND METHODS: This study enrolled 171 subjects, divided into two groups: healthy subjects and gingivitis patients. TNF- α (-308 G/A) gene polymorphism was analyzed by PCR-RFLP assay. Salivary and serum samples were used to measure cytokine levels through the ELISA technique. RESULTS: TNF- α (-308 G/A) polymorphism was shown to have a protective effect in carriers of the A/A genotype and allele A. The G/A genotype is associated with an increase in high-density lipoprotein cholesterol (HDL-C) levels in the gingivitis group. Healthy individuals had higher levels of salivary TNF- α and HDL-C, and increased salivary flow. Triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels were increased in the gingivitis group. No statistical differences were found in serum TNF- α levels. CONCLUSION: Our data demonstrate that the TNF- α -308 A/A genotype exerts a protective effect against gingivitis. Moreover, oral conditions are associated with some biochemical parameters.

A Review of the Antimicrobial Activity of Selenium Nanoparticles.

Antimicrobial resistance has become a severe problem for health systems worldwide, and counteractions are challenging because of the lack of interest of pharmaceutical companies in generating new and effective antimicrobial drugs. Selenium nanoparticles have attracted considerable interest in treating bacteria, fungi, parasites, and viruses of clinical importance due to their high therapeutic efficacy and almost zero generation of adverse effects. Some studies have revealed that the antimicrobial activity of these nanoparticles is due to the generation of reactive oxygen species, but more studies are needed to clarify their antimicrobial mechanisms. Other studies show that their antimicrobial activity is increased when the surface of the nanoparticles is functionalized with some biomolecules or when their surface carries a specific drug. This review addresses the existing background on the antimicrobial potential offered by selenium nanoparticles against viruses, bacteria, fungi, and parasites of clinical importance.

A Review of the Effects of Gold, Silver, Selenium, and Zinc Nanoparticles on Diabetes Mellitus in Murine Models.

Diabetes mellitus is a disease that presents great challenges for healthcare systems worldwide, and the identification of alternative therapies for the treatment of this disease is of vital importance. Metallic nanoparticles (gold, silver, and selenium) and metallic oxide (ZnO) have been studied in different areas such as medicine, biotechnology, the environment, and the food industry with promising results. In medicine, current research has revealed these nanoparticles' anti-diabetic properties thanks to the implementation of animal models. This review will address the existing antecedents and the effects of gold, silver, selenium, and zinc oxide nanoparticles in diabetes administered alone, functionalized with other molecules, or combined with drugs that have shown promising therapeutic effects. The anti-diabetic effects of these nanoparticles are related to the regulation of glucose, insulin, and lipid profiles. In addition, oxidative stress markers, liver and kidney markers, the reduction of inflammation, apoptosis of the pancreas, and the restoration of normal liver and kidney histology are also reported in the literature after using these nanoparticles. However, the therapeutic effects that these nanoparticles provide are limited due to the lack of specific protocols dictated by international organizations to evaluate the risks of using these nanoparticles.

Association of Obesity with Depressive Symptomatology, Eating Habits, Interleukin-8 and Cortisol in a Young Population.

Obesity is the result of a complex combination of psychological, biological, and environmental factors. In this work, we evaluate whether obesity is related to eating habits, depressive symptomatology, as well as interleukin-8 and cortisol. A descriptive cross-sectional study was carried out in 232 university students. All youths were surveyed to determine their eating habits and depressive symptomatology. Anthropometric measures and a blood sample were taken to determine its biochemical profile and its concentration of interleukin-8 and cortisol. The results show that interleukin-8 increase in the overfat group. The altered eating behaviors were frequent in the studied group; they were associated with the presence of obesity and the variation of interleukin-8 and cortisol. Besides, we found correlations of interleukin-8 with age, glucose, and lipid profile in the overfat group. In conclusion, these results indicate that high adiposity is related to changes in the concentrations of interleukin-8 and eating habits, confirming that obesity is the consequence of a complex network of various factors.

Alteration of cytokines in saliva of children with caries and obesity.

Caries and obesity are multifactorial diseases with inflammatory components, whose processes involve cells and molecules, such as cytokines. Therefore, the objective of this work was to compare the concentrations of IL-6, IL-8, IL-15, and IL-18 in the salivary samples of children with caries and obesity. The study was carried out with 80 children: 43 with a normal weight and 37 with obesity. The diagnosis of caries was carried out using the ICDAS system. Salivary samples were used to measure the cytokine levels via the ELISA technique. Our results show that children with obesity and dental cavities have high levels of IL-6 and IL-15. Similarly, obese children have elevated levels of these two cytokines, while children with cavitated carious lesions presented alterations in their concentrations of IL-6 and IL-8. In conclusion, our data suggest that IL-6 has a significant effect on both obesity and caries, although IL-8 is more related to caries, and IL-15 is more related to obesity.

Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is characterized by chronic inflammation, in which different types of immune cells participate, such as TH17 cells and Treg cells. The aim of this study was to determine the relationship between Treg and Th17 in patients with different times of T2DM progression. MATERIAL AND METHODS: Nineteen control subjects and 40 patients with T2DM were included. T2DM patients were classified into two groups: the first group consisted of twenty patients with less than10 years of disease progression (T2DM < 10), and the second group included 20 patients with a disease progression of 10 years or more (T2DM ≥ 10). Additionally, an analysis was performed according to the metabolic control, depending on HbA1c levels. The peripheral blood ratio of both Th17 and Treg cells was measured by standard flow cytometry protocols. RESULTS: No significant difference was found in Th17 cells of patients with T2DM < 10 or T2DM ≥ 10 and controls. With respect to CD4+CD25+FoxP3+ and CD4+CD25h Treg cells, a significant decrease was observed in patients with T2DM ≥ 10, mainly in patients with poor or moderate metabolic control. Statistical analysis performed in all patients with T2DM revealed a decrease in three cell subsets as well a negative correlation between Th17 cells and total cholesterol, CD4+CD25h cells with glucose and HbA1c levels, while a positive correlation was observed between CD4+CD25h cells and BMI. CONCLUSIONS: A decrease on both Treg and Th17 cell subsets in T2DM patients was observed suggesting that the metabolic decontrol and the progression time of T2DM could modify the proportions of Th17 and Treg cells.

Protein Expression Profile of Twenty-Week-Old Diabetic db/db and Non-Diabetic Mice Livers: A Proteomic and Bioinformatic Analysis.

Type 2 diabetes mellitus is characterized by insulin resistance in the liver. Insulin is not only involved in carbohydrate metabolism, it also regulates protein synthesis. This work describes the expression of proteins in the liver of a diabetic mouse and identifies the metabolic pathways involved. Twenty-week-old diabetic db/db mice were hepatectomized, after which proteins were separated by 2D-Polyacrylamide Gel Electrophoresis (2D-PAGE). Spots varying in intensity were analyzed using mass spectrometry, and biological function was assigned by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. A differential expression of 26 proteins was identified; among these were arginase-1, pyruvate carboxylase, peroxiredoxin-1, regucalcin, and sorbitol dehydrogenase. Bioinformatics analysis indicated that many of these proteins are mitochondrial and participate in metabolic pathways, such as the citrate cycle, the fructose and mannose metabolism, and glycolysis or gluconeogenesis. In addition, these proteins are related to oxidation⁻reduction reactions and molecular function of vitamin binding and amino acid metabolism. In conclusion, the proteomic profile of the liver of diabetic mouse db/db exhibited mainly alterations in the metabolism of carbohydrates and nitrogen. These differences illustrate the heterogeneity of diabetes in its different stages and under different conditions and highlights the need to improve treatments for this disease.

[Mechanisms of suppression of regulatory T-cells (Treg)]. / Mecanismos de supresión de las células T reguladoras (Treg).

An important feature of immunology is understanding how the immune system is able to discriminate between self and non-self. Regulatory T-cells (Treg) actively inhibit immune responses involved in the pathological and physiological responses, and, in consequence, contribute to the maintenance of homeostasis. The characterization of these regulatory T-cells has been controversial due to the lack of exclusive markers for their identification and isolation. The mechanisms that regulatory T-cells use to function are: cytokines, death cells, modullation of the microenvironment, and surface receptors. The immune system and Treg cells have been related to obesity and type 2 diabetes mellitus through the inflammatory process. In this work, we review the proposed markers for Treg cells, recent data on the mechanism used for the main function of Treg cells, immune regulation, and we conclude with the impact of these cells on obesity and type 2 diabetes mellitus.

Association analysis between -308G/A and -238G/A TNF-alpha gene promoter polymorphisms and insulin resistance in Mexican women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM. METHODS: This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α -308G/A and -238G/A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls (P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31-12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the -308G/A polymorphism (P = 0.022 and P = 0.043, respectively). CONCLUSIONS: Our results suggest that the G/G genotype of the TNF-α -308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.